RT Schedule Research Articles

Breast Cancer Adjuvant Radiotherapy and Chemotherapy Sequencing: Sequential, Concomitant, or What Else? A Comprehensive Review of the Adjuvant Combinations Journey.

Background: To date, in breast cancer (BC) treatment, adjuvant chemotherapy (A-CT) has preceded adjuvant radiotherapy (A-RT). In the last twenty years, the adjuvant treatment of BC has quickly evolved due to better knowledge of its molecular biology, genetic profile, and α/β ratio of 3/4 Gy for tumor and normal tissue radiosensitivity. Thus, new schedules with hypofractionated radiotherapy have been tested, and a third generation of A-CT has been introduced, raising the question of whether it is time to rethink the sequencing between these two approaches. Methods: In the last 20 years, many attempts have been made worldwide to optimize the best sequencing strategy between these two approaches in terms of sequential CT-RT and RT-CT and concomitant and sandwich modalities using drugs and schedules. This paper presents a comprehensive review of the state of the art, analyzing all the available studies to assess the sequencing between A-CT and A-RT with different generations of chemotherapy schedules. Results: More than 8000 patients from 30 studies treated with adjuvant chemotherapy and whole breast radiotherapy who were enrolled in randomized, retrospective, and prospective studies were analyzed. Sequential, concomitant, and sandwich modalities of chemotherapy with conventional or hypofractionated RT schedules from the most important studies were included. The most used sequence was adjuvant chemotherapy followed by conventional or hypofractionated radiotherapy. In the concomitant approach, i.v. CMF has been the most important adopted schedule, while the concomitant use of anthracyclines and taxanes with conventional or hypofractionated radiotherapy has been found to be more toxic. One study analyzed the benefit in terms of reducing adjuvant treatment time with upfront hypofractionated radiotherapy and third-generation chemotherapy. Conclusions: At present, the best sequencing strategy has not yet been defined. This comprehensive review is a journey among the most important randomized, retrospective, and prospective studies that highlights the past, current, and novel time sequencing proposals between A-CT and A-RT to assess the state of the art and provide useful information for future adjuvant approaches in breast cancer treatment.

A Comparative Study of Palliative Hypo-fractionated vs Conventional Fractionated Radiotherapy in Locally Advanced Non Small Cell Lung Cancer

Purpose: To compare the compliance, tumor response, quality of life and survival between a hypo-fractionated and a conventional fractionated RT schedule in locally advanced NSCLC patients. Materials and Methods: Total 50 patients with unresectable stage III NSCLC were given 3 cycle of neoadjuvant chemotherapy. After 3-4 weeks of completion of 3rd cycle, 25 patients received a total 17Gy in 2 fr (8.5Gy/fr) on day 1 and day 8 in study arm, 25 patients received a total 50 Gy in 25 fr (2Gy/fr) administered daily (5days/week) for 5 weeks. Disease response was evaluated by RECIST criteria at 1, 3 and 6 month. Then follow up was done after 1yr, 2yr and 3yr to evaluate the overall survival. Result: none of patients in both arms had complete response at any follow up. Locoregional disease control was observed in 18% & 27% in study and control arm respectively (p value>0.05). Median survival was 10 months and 12.5 months in study and control arm respectively which was not statistically significant. There was no statistically difference in grade of toxicities. OS rates at 1, 2 and 3years were 40%, 10% and 0% in study arm and 50%, 20% and 5% in control arm but difference in OS was not statistically significant. Conclusion: Many patients were lost to follow up in our study; although among the patients followed, we found to concluded that for improvement of quality of life in locally advanced NSCLC patients with poor PS and short life span, the palliative hypo-fractionated regimen of short duration (17Gy/2fr) could be considered as a reasonable alternative and also economically feasible & required shorter duration of stay in the hospital. In conclusion, large number of patients with strict follow up need to be done to ascertain the need and benefits of this palliative TRT.

PALC-02. PALLIATIVE RADIOTHERAPY FOR HAEMOSTASIS IN CHILDREN WITH CEREBRAL METASTATIC HAEMORRHAGE

Abstract BACKGROUND Among children, bleeding from brain metastases is rare. Bleeding could be caused by: cancer, treatments and chemotherapy/other drugs such as Bevacizumab, NSAIDs and anticoagulants. We report a case of brain RT after metastases bleeding. METHODS A 14-years-old boy with a negative previous medical history presented to the Emergency Department with seizures and loss of consciousness. Full-body CT scan revealed brain and renal haemorrhages and a right testicular lesion. Serum βhCG was 223,773 mIU/mL. Neurosurgical bleeding control and right orchiectomy were performed: the histopathology revealed a metastatic mixed non-seminomatous germ cell neoplasia of the testis. First-line chemotherapy (4 cycles of Cisplatin/Etoposide/Ifosfamide) and second-line treatments (Paclitaxel/Ifosfamide/Cisplatin and Gemcitabine/Paclitaxel/Oxaliplatin) were performed. Suddenly, he presented with left-sided hyposthenia and partial left hemibody seizure. CT scan revealed 2 haemorrhagic brain lesions, one in each hemisphere. Surgery was not feasible. We started anti-oedema and anti-epileptic therapy, and whole brain RT (WBRT, 36 Gy/12 fx, BEDα/β= 10 Gy= 46.8 Gy). After 5 days from the start, RT had a 7-day stop because of acute oedema and clinical deterioration. Fourth-line chemotherapy was administered with CarboPEB (1st of further 4 cycles), and then WBRT was restarted. At the end of WBRT a stereotactic RT boost to both the haemorrhagic lesions was delivered (20 Gy/10 fx, BEDα/β= 10 Gy= 24.0 Gy). As of today, eight months after the end of therapy, the patient is free from disease and βhCG is negative. CONCLUSION Palliative RT in children is a non-conventional indication, but potentially effective at providing rapid haemostasis, especially in selected cases (surgery not feasible/contraindicated, adult-type histologies, …) and it is ensuring a good tumor control and low-grade acute toxicities. Hypofractionation is suggested to balance patient comfort and treatment effectiveness, especially when life expectancy is short. The optimal RT schedule, dose and fractionations need to be further investigated.

DIPG-04. THE BENEFIT OF CRANIOSPINAL IRRADIATION (CSI) RESCUE IN PHASE 2 RANDOMIZED STUDY OF RADIOTHERAPY (RT), CONCOMITANT NIMOTUZUMAB AND VINORELBINE AND RE-IRRADIATION AT RELAPSE, VERSUS MULTIPLE ELECTIVE RADIOTHERAPY COURSES WITH CONCOMITANT VINORELBINE AND NIMOTUZUMAB FOR NEWLY DIAGNOSED CHILDHOOD AND ADOLESCENCE DIFFUSE INTRINSIC PONTINE GLIOMA (DIPG)

Abstract BACKGROUND This trial evaluated feasibility,response,PFS/OS of a randomization comparing two different RT schedules for DIPG while administering the same systemic treatment. We moreover evaluated the benefit of craniospinal irradiation(CSI) in case of disseminated(D) relapse. METHODS Patients: 2-21 years-old with at least radiologically verified DIPG (MRI blindly reviewed at diagnosis,every 12 weeks thereafter) and symptoms duration below 6 months. Biopsy required if atypical imaging, also allowed after adequate consensus.Vinorelbine 20 mg/m2+nimotuzumab 150 mg/m2 were administered weekly for 12; thereafter every other week until tumor progression or for up to 2 years. Standard(ST) arm was full brainstem/focal tumor site RT at total dose of 54Gy(1.8Gy/day); for local progression re-irradiation was proposed at 19.8Gy, in case of dissemination CSI at 36Gy was offered.Experimental(SP) arm included three elective courses of RT at defined time-points(36Gy, 19.8Gy and 19.8Gy) with reirradiation for relapse at 9 Gy/36 Gy as above described. Incidences of local(L) and D progression were assessed in a competing risk setting. RESULTS 55 patients were included from 4 Italian centers,27 in ST,30 males, median age 7.1 years. Median follow-up 39.1 months. Fifteen patients needed a shunt,13 during treatment;23 were biopsied,in 21 according to local protocols.22/23 tumors had H3.3K27 mutation. 53 relapsed, 34 L,13 D,6 L+D.Fifteen/19 with a D component receiving CSI had a median survival of 7.6 months after relapse, significantly higher than that of the 4 without CSI(median 2.9 months,P=0.020). Patients submitted to biopsies had more D(P=0.017) and less L progression(P=0.058). SP irradiation and any reirradiation at relapse were feasible and never produced significant radionecrosis.Median EFS/OS for the whole series were 8.4/14 months, respectively; not significantly different between patients with local vs. disseminated relapses. CONCLUSIONS Reirradiation, even if CSI, confirmed feasible and benefitted patients OS.Randomization results will be later reported.

Radiation Therapy in Non-Melanoma Skin Cancers: An Italian Survey on Behalf of the Italian Association of Radiotherapy and Clinical Oncology

AimsThe National Palliative Care and Interventional Radiotherapy Study Groups of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) carried out a survey whose aim was to obtain a "snapshot" of the real-world practice of nonmelanoma skin cancer (NMSC) treatments in Italy. Materials and methodsThe survey was conducted on SurveyMonkey's online interface and was sent via e-mail to our society Radiation Oncologists. ResultsFifty-eight Italian radiation oncologists (ROs), representing 54 centers, answered the survey. Thirteen percent of the ROs declared they treat fewer than 10 NMSC lesions annually, 36% treat between 11 and 20, and 51% treat more than 20 lesions annually. Interventional radiotherapy (IRT) was offered by 25% of the ROs, and every case was reportedly discussed by a multidisciplinary team (71%). Electrons (74%), volumetric modulated arc therapy (V-MAT) (57%), three-dimensional conformal radiotherapy (3D-CRT) (43%), and IRT (26%) were the main treatment options. With external beam radiotherapy (EBRT), 46 and 53 different RT schedules were treated for curative and palliative intent, respectively; whereas for IRT, there were 21 and 7 for curative and palliative intent, respectively. The most popular EBRT curative options were 50–70.95/22–35 fractions (fx) and 50–70 Gy/16-20fx and for EBRT palliative settings, 30Gy/10fx, and 20–35Gy/5fx. For IRT, the most popular curative options were 32–50Gy/8-10fx and 30–54Gy/3-5fx, whereas 30Gy/6fz was the palliative option. Less than 10 re-RT cases were reported in one year in 42.5%, 11–20 cases in 42.5%, and >20 cases annually in 15%. Electrons (61%), VMAT (49%), and BRT (25%) were the most widely used approaches: 20–40Gy in 10fx and 20–25Gy in 5fx were the recommended fractionations. ConclusionThe survey shows a variegated reality. A national registry with more detailed data could help in undercover its causes.

Toxicity profile and Patient-Reported outcomes following salvage Stereotactic Ablative Radiation Therapy to the prostate Bed: The POPART multicentric prospective study

BackgroundWhile SBRT to the prostate has become a valuable option as a radical treatment, limited data support its use in the postoperative setting. Here, we report the updated results of the multicentric Post-Prostatectomy Ablative Radiation Therapy (POPART) trial, investigating possible predictors of toxicities and patient-reported outcomes. MethodsPatients with PSA levels between 0.1–2.0 ng/mL after radical prostatectomy received Linac-based SBRT to the prostate bed in five fractions every other day for a total dose of 32.5 Gy (EQD21.5 = 74.3 Gy). Late toxicity was assessed using CTCAE v.5 scale, while EPIC-CP, ICIQ-SF, IIEF 5 questionnaires and PSA levels measured quality of life and biochemical control. Pre- and post-treatment scores were compared using a paired t-test, with MID established at > 0.5 pooled SD from the baseline. A logistic regression analysis was performed to evaluate potential associations between specific patient/tumor/treatment factors and outcome deterioration. ResultsFrom April 2021 to April 2023 a total of 50 pts were enrolled and treated. Median follow-up was 12.2 (3–27) months. No late ≥ G2 GI or GU toxicity was registered. Late G1 urinary and rectal toxicities occurred in 46 % and 4 % of patients, respectively. Among 47 patients completing all EPIC-CP domains, four (9 %) showed worsened QoL, and eleven (26 %) developed erectile dysfunction correlating with PTV D2% (P = 0.032). At Multivariate analysis bladder wall D10cc independently correlated with late G1 GU toxicity (P = 0.034). Median post-treatment PSA nadir was 0.04 ng/mL (0.00 – 0.84). At the last follow-up, six patients presented with biochemical failure, including two nodal relapses. ConclusionsOur findings show that post-prostatectomy SBRT did not result in increased toxicity nor a significant decline in QoL measures, thus showing that it can be safely extended to the postoperative setting. Long-term follow-up and randomized comparisons with different RT schedules are needed to validate this approach.

Managing RT Schedules of Early-Stage Breast Cancer Patients with a Genetic-Dosimetric Validated Model for Late Fibrosis

Define a multifactorial risk prediction model for RT-induced fibrosis and investigate the benefit of a personalized approach for breast cancer (BC) patients (pts) treated with whole breast RT. In a previous study, we confirmed the predictive role of 30 SNPs from the literature and built an interaction aware Polygenic Risk Score (PRS, following the methods from Franco RO 2021) for Late Fibrosis (FG2+) on a cohort of 1500 pts from the REQUITE EU/USA prospective observational study. The PRS weights the radiosensitive (RS) and radioresistant (RR) genetic components and can be included in NTCP models. In a subgroup from the same cohort (390 pts), we have also confirmed an NTCP model based on biologically Equivalent Uniform Dose (BEUD) from PTV DVHs for pts treated at 40-50 Gy and no RT boost. Here, we combine PRS and BEUD into a sigmoid model allowing PRS to modulate BEUD50 (BEUD leading to 50% FG2+), i.e., we permitted a personalized BEUD50. We can also consider this as translating the PRS into a personalized equivalent BEUD, which is added/subtracted to the treatment BEUD. We evaluated model performances through ROC-AUC, calibration plot and Precision-Recall AUC. A total of 381 pts had complete dosimetric/genetic data, prescribed dose 40-50 Gy, and no fibrotic alteration at RT start. We scored FG2+ in 87 pts (23%). PRS ranged from -13 (more RR pts) to 7 (more RS), and a unit in PRS corresponds to 5.3 Gy BEUD or 3 Gy in EQ EUD2 Gy. Table 1 summarizes model performances, with details for subgroups below/above the quartiles I/III of the BEUD distribution. The PRS-only model correctly describes the toxicity rates in the whole population (calibration slope/offset = 0/1). Still, it overestimates/underestimates the absolute risks in the low/high dose ranges. The integrated model improves AUC-ROC and AUC-PRC by 5% and 10% and guarantees a better calibration in pts receiving low/high BEUD to the PTV. We developed a multifactorial model for FG2+ based on two previously validated models and reported the improvement against single-factor models. The BEUD+PRS model is suitable for assisting clinicians in managing early-stage BC pts. The number of fractions or the daily dose could be reduced for RS pts. The integrated model resulted in a possible quantitative tool for driving the planning decision process. Also, it showed a better performance in the high BEUD region, suggesting the potential value of its extension toward RT including boost or ultra hypofractionation. We are testing this extension in the whole REQUITE cohort.

Integrating radiation therapy with CDK4/6 inhibitors for breast cancer: A systematic review and meta-analysis of toxicity.

e13075 Background: Over the past years, the treatment landscape of breast cancer (BC) has significantly evolved. Several new anticancer agents entered clinical use. Among them CDK4/6i have revolutionised both curative and advanced BC scenarios. The availability of new drugs raises the crucial question on how to integrate them with local and regional treatments. Strong levels of evidence on the safety profile of CDK4/6i in combination with different RT techniques or schedules are currently missing. We aim to systematically review and summarise the published data on the safety profile of palliative and ablative RT combined with CDK4/6i in early and metastatic BC settings. Methods: A literature search (PUBMED/MedLine, Embase, and Cochrane databases) was conducted to identify original studies on the safety profile of the combination of CDK4/6i with RT. This systematic review and meta-analysis project is part of the ESTRO Guidelines Committee consensus recommendations on integration of RT with targeted treatments for breast cancer, an initiative developed by a multidisciplinary Core Group and Expert Panel of medical, clinical, radiation oncologists, preclinical specialists, and patient advocates. Results: Eleven articles finally met all eligible criteria and were included in the meta-analysis. Data could not be collected in the adjuvant setting due to lack of data in the current literature. Pooling data of the included studies show a moderate incidence of hematological toxicities grade 3+ (21.0 %) and a very low-grade 3+ non-hematological toxicity were observed. Conclusions: The safety profile of CK4/6i and RT combination is acceptable. However, international consensus guidelines regarding the safety issue of CDK4/6i and RT combination for breast cancer are warranted.

PO-1514 SBRT for clinically localized prostate cancer: a propensity scores analysis between two RT schedules

PO-1514 SBRT for clinically localized prostate cancer: a propensity scores analysis between two RT schedules

Selecting a TNT Schedule in Locally Advanced Rectal Cancer: Can We Predict Who Actually Benefits?

Many consider the standard of care for locally advanced rectal cancer (LARC) to be preoperative chemoradiotherapy, radical surgery involving a total mesorectal excision, and post-operative adjuvant chemotherapy based on the pathology of the specimen. The poor impact on distant control is a major limitation of this strategy, with metastasis rates remaining in the 25-35% range and recovery after radical surgery leading to reluctance with prescription and inconsistent patient compliance with adjuvant chemotherapy. A second limitation is the low rate of pathologic complete response (pCR) (around 10-15%) despite multiple efforts to potentiate preoperative chemoradiation regimens, which in turn means it is less effective at achieving non-operative management (NOM). Total neoadjuvant treatment (TNT) is a pragmatic approach to solving these problems by introducing systemic chemotherapy at an early timepoint. Enthusiasm for delivering TNT for patients with LARC is increasing in light of the results of published randomized phase III trials, which show a doubling of the pCR rate and a significant reduction in the risk of subsequent metastases. However, there has been no demonstrated improvement in quality of life or overall survival. A plethora of potential chemotherapy schedules are available around the radiotherapy component, which include preoperative induction or consolidation with a range of options (FOLFOXIRI, FOLFOX, or CAPEOX,) and a varying duration of 6-18 weeks, prior to long course chemoradiation (LCCRT) or consolidation NACT following short-course preoperative radiation therapy (SCPRT) using 5 × 5 Gy or LCCRT using 45-60 Gy, respectively. The need to maintain optimal local control is a further important factor, and preliminary data appear to indicate that the RT schedule remains a crucial issue, especially in more advanced tumors, i.e., mesorectal fascia (MRF) invasion. Thus, there is no consensus as to the optimum combination, sequence, or duration of TNT. The selection of patients most likely to benefit is challenging, as clear-cut criteria to individuate patients benefiting from TNT are lacking. In this narrative review, we examine if there are any necessary or sufficient criteria for the use of TNT. We explore potential selection for the individual and their concerns with a generalized use of this strategy.

Extreme hypofractionated stereotactic radiotherapy for elderly prostate cancer patients: side effects preliminary analysis of a phase II trial.

Aim of this study is to evaluate safety and efficacy of SBRT in elderly patients affected by localized prostate cancer (PC). Men aged 70years or older were enrolled and analyzed. The SBRT schedule was 35Gy in 5 fractions administered in 1-2weeks. According to risk group, androgen deprivation therapy (ADT) was prescribed. Urinary symptoms were evaluated at baseline using the International Prostate Symptom Score (IPSS). Genitourinary (GU) and gastrointestinal (GI) toxicities were assessed at the end of treatment, 2weeks after SBRT and during follow-up using the Common Terminology Criteria for Adverse Events (CTCAE). PSA values were recorded before treatment and during follow-up as biochemical response criteria. Between 07/2019 and 09/2021, 111 patients were enrolled. Median age was 77years. At the end of treatment, no acute GU/GI toxicities ≥ G2 were observed. At 2-3weeks after treatment, 3 patients reported G2 GU toxicity, while 14 patients referred G2 GI toxicity. During the last follow up, 26 and 2 patients reported, respectively, G1 and G2 GU toxicity, while 22 and 1 cases described, respectively, G1 and G2 GI toxicity. No late toxicities ≥ G3 were recorded. GU toxicity is related to absence of urethra sparing, increasing PTV volume, Dmax PTV and IPSS; GI toxicity is related to RT schedule (each other day is better than consecutive day), Dmax rectum and IPSS, At a median follow-up of 24months, excellent biochemical disease control was achieved in all cases with median PSA of 0.5ng/ml. SBRT in elderly patients affected by PC is feasible and well tolerated with excellent biochemical disease control. Longer follow-up is needed to assess late toxicity profile and long-term clinical outcome.

Changing pattern of radiation therapy for bone metastases in an Australian population-based cohort of men with prostate cancer.

To evaluate the pattern of use of single-fraction conformal radiation therapy (SF-RT) and advanced radiation therapy techniques (ART), including stereotactic body radiation therapy (SBRT), for management of bone metastases (BM) in a population-based cohort of Australian men with prostate cancer (PCa) PATIENT AND METHODS: We reviewed men with metastatic PCa who received RT for BM between 2012 and 2017 as captured in the statewide Victorian Radiotherapy Minimum Data Set (VRMDS). The primary outcomes were: proportion of RT courses using SF-RT and ART. The Cochrane-Armitage test for trend was used to evaluate the changing pattern of SF-RT and ART over time. Multivariate analyses were used to identify factors associated with the primary outcomes RESULTS: Of the 4,324 courses of palliative RT for BM, 767 (17.7%) were SF-RT, and 615 (14.2%) were ART. There was no evidence of change in SF-RT use over time (P-trend=0.13). In multivariate analyses, increasing age at RT, site of BM (rib, shoulder, pelvis, and extremities), patients' area of residence (regional and remote), and treatment in public and metropolitan centres were associated with increased likelihood of SF-RT use. There was marked increase in ART use from 0.2% in 2012 to 24% in 2017 (11% intensity modulated RT, 13% SBRT) (P-trend<0.001). In multivariate analyses, younger age at RT, site of BM (rib and pelvis), higher socioeconomic status, and treatment in private and metropolitan centres were associated with increased likelihood of ART use. SF-RT continues to be a clear minority of RT schedules employed in management of BM in PCa, and the adoption of SF-RT use should be encouraged in men with limited prognosis. There has been increasing use of ART, especially SBRT, for BM in PCa over time, and we expect this will continue to increase in the era of metastatic-directed treatment for PCa.

Tumor Microenvironment Modifications Recorded With IVIM Perfusion Analysis and DCE-MRI After Neoadjuvant Radiotherapy: A Preclinical Study.

PurposeNeoadjuvant radiotherapy (NeoRT) improves tumor local control and facilitates tumor resection in many cancers. Some clinical studies demonstrated that both timing of surgery and RT schedule influence tumor dissemination, and subsequently patient overall survival. Previously, we developed a pre-clinical model demonstrating the impact of NeoRT schedule and timing of surgery on metastatic spreading. We report on the impact of NeoRT on tumor microenvironment by MRI.MethodsAccording to our NeoRT model, MDA-MB 231 cells were implanted in the flank of SCID mice. Tumors were locally irradiated (PXI X-Rad SmART) with 2x5Gy and then surgically removed at different time points after RT. Diffusion-weighted (DW) and Dynamic contrast enhancement (DCE) MRI images were acquired before RT and every 2 days between RT and surgery. IntraVoxel Incoherent Motion (IVIM) analysis was used to obtain information on intravascular diffusion, related to perfusion (F: perfusion factor) and subsequently tumor vessels perfusion. For DCE-MRI, we performed semi-quantitative analyses.ResultsWith this experimental model, a significant and transient increase of the perfusion factor F [50% of the basal value (n=16, p<0.005)] was observed on day 6 after irradiation as well as a significant increase of the WashinSlope with DCE-MRI at day 6 (n=13, p<0.05). Using immunohistochemistry, a significant increase of perfused vessels was highlighted, corresponding to the increase of perfusion in MRI at this same time point. Moreover, Tumor surgical resection during this peak of vascularization results in an increase of metastasis burden (n=10, p<0.05).ConclusionSignificant differences in perfusion-related parameters (F and WashinSlope) were observed on day 6 in a neoadjuvant radiotherapy model using SCID mice. These modifications are correlated with an increase of perfused vessels in histological analysis and also with an increase of metastasis spreading after the surgical procedure. This experimental observation could potentially result in a way to personalize treatment, by modulating the time of surgery guided on MRI functional data, especially tumor perfusion.

Comparative Study of Two Thoracic Radiotherapy Schedules for Palliation of Symptom, Radiological Response and Acute Toxicities in Advanced Non-small Cell Lung Cancer

Aim: To compare the effect of two RT schedules for thoracic palliation in advanced NSCLC patients (30 Gy in 10 fractions over two weeks and 27 Gy in 6 fractions over three weeks, 2 fractions per week) on pulmonary symptoms, radiological response of the primary thoracic tumour, pulmonary functions and acute toxicities. Material and method: A hospital based quantitative prospective follow-up study. Total 104 advanced NSCLC patients were randomized into two fractionation arms. Evaluation was done pretreatment and 4 weeks after end of RT. Symptoms palliation and radiological response to RT &amp; radiation pneumonitis were assessed by using RTOG 4-point scale and Revised (RECIST) guideline version 1.1 respectively. Radiotherapy was given by Cobalt-60 teletherapy machine. Results: Total 96 patients were evaluated for symptom palliation, radiological response and acute toxicities. The percentage of patients achieving symptom palliation was slightly higher in the control arm. At 1st month of follow-up, 16.67% &amp; 18.75% patients in Study &amp; control arm showed PR. Post-RT mean FVC and FEV1 showed a tendency for improvement in both mean FVC and FEV1 in compare to baseline. Treatment was well tolerated both arms. Grade I nausea and vomiting developed in 43% and 37.5% patients in Study and Control Arm respectively. 58% &amp; 39% patients developed Grade 1 radiation pneumonitis as cough &amp; dyspnea in study and control arms respectively. Grade 2 radiation pneumonitis was developed in 2 patient of study arm at 3rd week of follow-up but they lost follow up. Around 31% patients developed Grade1 esophagitis as dysphagia in both arms at 1 week of follow-up which was reduced up to 7% by 2nd week. A very few patients developed grade1 skin reaction as dermatitis in 1st week of treatment. The difference in symptom palliation, radiological response, pulmonary functions and acute toxicities in both arms was not statistically significant. Conclusion: The two RT fractionation schedules showed equal efficacy in terms of symptoms palliation, radiological response of the primary thoracic tumor, pulmonary functions and acute toxicities. Thus the 27 Gy/6 fractionation arm appears preferable compared to 30 Gy/10 arm to minimize the patients’ visits and load on the machines.

Synchronous bilateral breast cancer treated with a 3-week hypofractionated radiotherapy schedule: clinical and dosimetric outcomes.

Background and purposeSynchronous bilateral breast cancer (SBBC) accounts for 1–3.5% of breast cancer patients. The aim of this study was to evaluate dosimetric issues, clinical outcomes, and acute toxicities for SBBC patients receiving synchronous bilateral hypofractionated radiotherapy (SBHRT) and to compare them with patients treated with synchronous bilateral normofractionated RT schedule (SBNRT).Materials and methodsFrom April 2016 to March 2020, 39 SBBC patients were referred to our institution. Patients were divided according to their prescription dose: Group A: 50 Gy/25fx (fractions), B: 60–64 Gy/25fx, C: 40.05 Gy/15fx; D: 48 Gy/15fx. Toxicity was evaluated using Common Terminology Criteria for Adverse Events (CTCAE)v.5.0.Results34 patients were finally evaluated. Median follow-up was 24 months for NF schedule and 9 months for HF schedule. In the HF schedule, no acute side-effects > G2 were observed and no dermatitis was reported in 6th month´s assessments. 95% of patients have no evidence of disease and only 1 patient presented local relapse in the first mammography after RT. No distant failures or deaths were observed. Regarding dosimetric issues, the inter-patient average Dmean for the heart was: Group A: 5.0 Gy (4.6–5.5), Group B: 4.4 Gy (4.1–5.4), Group C: 4.8 Gy (4.5–5.1) and Group D: 5.3 Gy (4.4–5.6). For the lungs, the inter-patient average Dmean was: Group A: 10.8 Gy (9.8–12.2), Group B: 11.5 Gy (11.3–12), Group C: 9.8 Gy (9.3–10.5) and Group D: 10.5 Gy (10–11.3).ConclusionsThis is the first study reporting the safety, feasibility, and tolerability of 40.05 Gy/15fx over 3 weeks for the treatment of SBBC patients. Further study with larger accrual is mandatory.

Comparing hypofractionated and conventionally fractionated whole breast irradiation for patients with ductal carcinoma in situ after breast conservation: a propensity score-matched analysis from a national multicenter cohort (COBCG-02 study).

Randomized trials confirmed the efficacy and the safety of hypofractionated whole breast irradiation (HF-WBI) in patients with early-stage breast cancer. However, the role of HF-WBI in patients with DCIS after breast conserving surgery has not yet been clearly established in prospective randomized trials. The aim of this study was to evaluate if HF-WBI can be considered comparable to conventionally fractionated (CF)-WBI in DCIS patients. The analysis included DCIS patients from four Italian centers treated with CF-WBI 50Gy/25 fractions or HFRT 40.5Gy/15 fractions, without tumor bed boost. A propensity score matching (PSM) analysis was performed using a logistic regression that considered age, grading, presence of necrosis, resection margin status and adjuvant endocrine therapy. Five hundred twenty-seven patients was included (367 in the CF-WBI-group and 160 in the HR-WBI group). After 1:1 matching, 101 patients were allocated to the CF-WBI-group and 104 to the HF-WBI group. No correlation was observed between the type of RT schedule and LRFS (HR 1.68, 95% CI 0.82-3.45; p = 0.152). After PSM, no statistical difference was observed between the two RT group (HR 1.11, 95% CI 0.40-3.04; p = 0.833), with 3- and 5-years LRFS rates of 100% and 97.9% for CF-WBI and 95.6% and 94% for HF-WBI. A short course of radiation therapy seems to be comparable to CF-WBI in terms of clinical outcomes. These data support the use of hypofractionated schedules in DCIS patients, but considering the remaining uncertainties.

Combined radiotherapy and immunotherapy in urothelial bladder cancer: harnessing the full potential of the anti-tumor immune response.

PurposeRadiotherapy (RT), as part of trimodal therapy, is an attractive alternative treatment in patients with urothelial muscle-invasive bladder cancer (MIBC). There is accumulating evidence suggesting the immunomodulatory effects of RT and its potential synergy when combined with immunotherapy. The aim of this review was to report on the most recent advances on this combination, including the mechanisms of RT immunomodulation, practical approach to combining RT and immunotherapy, and ongoing clinical trials in bladder cancer.MethodsUsing the PubMed database, we identified articles published between March 2004 and April 2020 on the combination of RT with immunotherapy in localized or metastatic MIBC. A search of the Clinicaltrials.gov and Clinicaltrialsregister.eu/ retrieved ongoing clinical trials on the topic as well.ResultsCombination of RT with immunotherapy leads to immunogenic cell death and an increase in immune markers thus leading to improved tumor control. For localized MIBC, there are safety concerns related to the use of concurrent immunotherapy with hypofractionated RT, thus neoadjuvant or adjuvant immunotherapy is preferred. In the metastatic setting, the combination of multi-site RT with SBRT-like doses (≥ 6 Gy per fraction) and concurrent immunotherapy seems most efficacious at harnessing the abscopal effect. At least 25 clinical trials combining immunotherapy and RT in MIBC are currently ongoing and will answer pending questions on safety, efficacy, and practical considerations on RT scheduling, fractionation, and targets volumes.ConclusionRT has the potential to synergize with immunotherapy to improve oncological outcomes in patient with localized or metastatic MIBC. Clinical trials results are eagerly awaited.

Phase III Randomized Study of Induction Chemotherapy Followed by Definitive Radiotherapy + Cetuximab Versus Chemoradiotherapy in Squamous Cell Carcinoma of Head and Neck: The INTERCEPTOR-GONO Study (NCT00999700)

Objectives: Induction chemotherapy followed by cetuximab and RT (IBRT) (Arm A) was compared to cisplatin/RT (CRT) (Arm B) in a randomized phase III study. Patients and Methods: Naïve patients with stage III-IVa, histologically proven locally advanced head and neck cancer (LASCCHN) were eligible. Arm A (IBRT): 3 TPF induction followed by cetuximab-RT (equivalent daily dose 2 Gy up to 70 Gy); Arm B: 3 cisplatin concurrent with the same RT scheduling. Due to slow accrual and incomplete data collection a futility analysis was performed. Results: 236/282 patients were evaluable. Therefore, no formal analyses can be made between the two arms. OS was 45.2/53.6 months in Arm A/B. Complete responses were achieved in 64% of patients in both arms. Neutropenia and skin toxicity were significantly worse in Arm A and body weight loss was significantly worse in Arm B. Compliance with the planned drug administration was higher in Arm B (p = 0.0008). Conclusion: The study suggests that IBRT and CRT have similar efficacy, activity and toxicity.

850PD - Benefit of prostate radiotherapy for patients with lymph node only or < 4 bone metastasis and no visceral metastases: Exploratory analyses of metastatic site and number in the STAMPEDE “M1|RT comparison”

BackgroundProstate radiotherapy (PRT) with androgen deprivation therapy (ADT) is now recommended as a first line option for de-novo low burden metastatic prostate cancer. In the STAMPEDE “M1|RT comparison” metastatic burden was a determinant of benefit, based on pre-specified prognostic criteria. We have now performed exploratory analyses of metastases as defined by site and number to improve prediction of treatment benefit from PRT. MethodsPatients (pts) randomized to the ADT (± docetaxel) vs PRT + ADT (± docetaxel) were studied. Metastatic site, distribution and number were evaluated based on conventional imaging and used to explore treatment effects to refine the metastatic burden definition. Results focused on the trial’s key outcome measures: overall (OS) & failure-free survival (FFS), analysed using standard survival analysis methods. HR<1 indicates benefit associated with PRT + ADT (±docetaxel) over ADT (±docetaxel). ResultsFollowing exclusions (imaging unavailable for central review, n=122), 1939 pts randomized in “M1|RT comparison” were included. Of these, 181 pts had only lymph node (LN) mets, 1587 had bone (±LN) mets and 171 had other visceral mets (±bone/LN). Baseline characteristics such as age (median 68 years), PSA (median 98ng/ml) were balanced between the arms. In LN only pts, PRT improved OS (HR=0.62, 95%CI 0.35-1.09) & FFS (HR=0.64, 95%CI 0.43-0.96). In bone (±LN) pts with <4 bone mets regardless of bone met location, PRT improved OS (HR=0.65, 95% CI 0.47 – 0.92) & FFS (HR=0.58, 95% CI 0.46 – 0.73). No such evidence of benefit was found in pts with visceral mets (OS: HR=0.92, 95%CI 0.58 – 1.45) or bone (±LN) pts with ≥4 bone mets (OS: HR=1.11, 95%CI 0.92 – 1.33). In the refined low met burden subgroup of pts with only LN or<4 bone mets (±LN), PRT improved OS (HR=0.62, 95%CI 0.46 – 0.83) & FFS (HR=0.57, 95%CI 0.47 – 0.70). Within the low met burden subgroup there was no evidence of heterogeneity in OS & FFS (all interaction p-value >0.1) for baseline factors such as age, N stage, Gleason score, RT schedule or docetaxel use. ConclusionsProstate RT + ADT (± docetaxel) improved OS & FFS in pts with only LN or<4 bone mets (±LN) regardless of location. Clinical trial identificationNCT00268476. Legal entity responsible for the studyMedical Research Council-Clinical Trials Unit and University of Manchester. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Supervisory Control Approach and its Symbolic Computation for Power-Aware RT Scheduling

Safety-critical systems implemented on multicore platforms need to satisfy stringent power dissipation constraints such as thermal design power (TDP) thresholds used by chip manufacturers. Power dissipation beyond TDP may trigger dynamic thermal management (DTM) in order to ensure thermal stability of the system. However, the application of DTM makes the system susceptible to higher unpredictability and performance degradations for real-time tasks. This paper proposes a formal scheduler synthesis framework that guarantees adherence to a system level peak power constraint while allowing optimal resource utilization in multicores. Our proposed framework makes use of supervisory control of timed discrete event systems as the underlying formalism. All steps starting from individual models to construction of the scheduler have been implemented through binary decision diagram based symbolic computation, so that the state-space complexity associated with the framework may be controlled. Furthermore, the synthesis framework has been extended to handle tasks with phased execution behavior. Conducted experiments have shown promising results and indicate to the practical efficacy of our approach.